This research project, presented as a "fast-track" SBIR proposal, deals with a new gene expression-based approach to the diagnosis and biological characterization of lung cancer in current and former smokers being evaluated for the possible diagnosis of lung cancer. Allegro Diagnostics is developing a portfolio of lung cancer biomarker products that are based on the principle that inhaled substances, cigarette smoke in particular, cause a "field of injury" throughout the lungs and airways, and that the global gene expression measured in easily accessible large airway epithelial cells obtained at bronchoscopy reflects biologic events occurring in the distal lung, where cancer develops. The first of these products, and the focus of this SBIR proposal, is BronchoGen, an 80 probe-set biomarker of lung cancer in current or former smokers. The immediate goals of the SBIR proposal are to evaluate the effect of new and improved reagents that have appeared in the past year on the BronchoGen test characteristics, to transfer the BronchoGen test to a commercial laboratory from the academic laboratory in which it was developed, and are to further validate the biomarker's accuracy, sensitivity, and specificity in a sample of 400 patients. The ultimate product of these studies will be a CLIA-approved lung cancer biomarker that will be submitted for FDA approval. Multiple sites throughout the country and two high-volume international sites will provide samples of bronchial epithelial cells from patients in whom bronchoscopy is being done to evaluate the possibility that a patient has lung cancer. Airway epithelial cell samples will be placed in a new RNA preservative that is effective when stored at room temperature for several weeks, sent by Federal Express to a commercial laboratory specializing in gene expression array studies, and CEL file results transported to Allegro Diagnostics for analysis and correlation with a computerized database that stores important clinical data, including ultimate diagnosis, the clinical process of diagnostic evaluation, staging of the cancer (if present), cell type and ultimate outcome. The initial product of these studies, BronchoGen", will reduce the costs and risks of unnecessary diagnostic procedures diagnosis, and risks of invasive procedures, and the amount of time between the suspicion of lung cancer and cancer diagnosis, by avoiding additional diagnostic procedures that often occur after non-diagnostic bronchoscopy. With BronchoGen", physicians will receive a lung cancer 'present or absent'statement, together with a statistical explanation of the biomarkers positive and negative predictive value and accuracy and sensitivity. The project goals of developing more timely and accurate diagnostics for lung cancer are directly aligned with NCI's mission to reduce the burden and eliminate adverse outcomes of cancer. PUBLIC HEALTH RELEVANCE: Allegro Diagnostics is developing a "toolbox" of products focused on the diagnosis and treatment of lung cancer, the leading cause of cancer death in the United States and the world. The focus of this SBIR, and the 1st of these products, is BronchoGen, a gene-expression based biomarker for use in patients undergoing bronchoscopy for the diagnosis of lung cancer. BronchoGen will decrease the amount of time between suspicion of lung cancer and lung cancer diagnosis, and will reduce the costs of diagnosis, treatment, and screening programs in people at high risk for the disease.